PMID- 23431040
OWN - NLM
STAT- MEDLINE
DCOM- 20130610
LR  - 20130417
IS  - 1537-6613 (Electronic)
IS  - 0022-1899 (Linking)
VI  - 207
IP  - 10
DP  - 2013 May 15
TI  - Regulation of chemokines, CCL3 and CCL4, by interferon gamma and nitric oxide 
      synthase 2 in mouse macrophages and during Salmonella enterica serovar 
      typhimurium infection.
PG  - 1556-68
LID - 10.1093/infdis/jit067 [doi]
AB  - BACKGROUND: Interferon gamma (IFN-gamma) increases the expression of multiple genes and 
      responses; however, the mechanisms by which IFN-gamma downmodulates cellular 
      responses is not well understood. In this study, the repression of CCL3 and CCL4 
      by IFN-gamma and nitric oxide synthase 2 (NOS2) in macrophages and upon Salmonella 
      typhimurium infection of mice was investigated. METHODS: Small molecule 
      regulators and adherent peritoneal exudates cells (A-PECs) from Nos2(-/-)mice 
      were used to identify the contribution of signaling molecules during 
      IFN-gamma-mediated in vitro regulation of CCL3, CCL4, and CXCL10. In addition, 
      infection of bone marrow-derived macrophages (BMDMs) and mice (C57BL/6, 
      Ifn-gamma(-/), and Nos2(-/-)) with S. typhimurium were used to gain an understanding 
      of the in vivo regulation of these chemokines. RESULTS: IFN-gamma repressed CCL3 and 
      CCL4 in a signal transducer and activator of transcription 1 (STAT1)-NOS2-p38 
      mitogen activated protein kinase (p38MAPK)-activating transcription factor 3 
      (ATF3) dependent pathway in A-PECs. Also, during intracellular replication of S. 
      typhimurium in BMDMs, IFN-gamma and NOS2 repressed CCL3 and CCL4 production. The 
      physiological roles of these observations were revealed during oral infection of 
      mice with S. typhimurium, wherein endogenous IFN-gamma and NOS2 enhanced serum 
      amounts of tumor necrosis factor alpha and CXCL10 but repressed CCL3 and CCL4. 
      CONCLUSIONS: This study sheds novel mechanistic insight on the regulation of CCL3 
      and CCL4 in mouse macrophages and during S. typhimurium oral infection.
FAU - Chandrasekar, Bhagawat
AU  - Chandrasekar B
AD  - Department of Biochemistry, Indian Institute of Science, Bangalore 560012, India.
FAU - Deobagkar-Lele, Mukta
AU  - Deobagkar-Lele M
FAU - Victor, Emmanuel S
AU  - Victor ES
FAU - Nandi, Dipankar
AU  - Nandi D
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20130221
PL  - United States
TA  - J Infect Dis
JT  - The Journal of infectious diseases
JID - 0413675
RN  - 0 (Activating Transcription Factor 3)
RN  - 0 (Ccl3 protein, mouse)
RN  - 0 (Chemokine CCL3)
RN  - 0 (Chemokine CCL4)
RN  - 0 (Chemokine CXCL10)
RN  - 0 (Cxcl10 protein, mouse)
RN  - 0 (STAT1 Transcription Factor)
RN  - 0 (Stat1 protein, mouse)
RN  - 0 (Tumor Necrosis Factor-alpha)
RN  - 82115-62-6 (Interferon-gamma)
RN  - EC 1.14.13.39 (Nitric Oxide Synthase Type II)
RN  - EC 1.14.13.39 (Nos2 protein, mouse)
RN  - EC 2.7.11.24 (p38 Mitogen-Activated Protein Kinases)
SB  - IM
MH  - Activating Transcription Factor 3/genetics/metabolism
MH  - Animals
MH  - Chemokine CCL3/genetics/*metabolism
MH  - Chemokine CCL4/genetics/*metabolism
MH  - Chemokine CXCL10
MH  - Gene Expression Regulation
MH  - Interferon-gamma/*metabolism
MH  - Macrophages/metabolism
MH  - Mice
MH  - Mice, Inbred C57BL
MH  - Mice, Knockout
MH  - Nitric Oxide Synthase Type II/genetics/*metabolism
MH  - STAT1 Transcription Factor/genetics/metabolism
MH  - Salmonella Infections, Animal/*immunology
MH  - Salmonella typhimurium/metabolism/pathogenicity
MH  - Stem Cells/metabolism
MH  - Tumor Necrosis Factor-alpha/blood
MH  - p38 Mitogen-Activated Protein Kinases/genetics/metabolism
EDAT- 2013/02/23 06:00
MHDA- 2013/06/12 06:00
CRDT- 2013/02/23 06:00
PHST- 2013/02/23 06:00 [entrez]
PHST- 2013/02/23 06:00 [pubmed]
PHST- 2013/06/12 06:00 [medline]
AID - jit067 [pii]
AID - 10.1093/infdis/jit067 [doi]
PST - ppublish
SO  - J Infect Dis. 2013 May 15;207(10):1556-68. doi: 10.1093/infdis/jit067. Epub 2013 
      Feb 21.